OUR MAIN OBJECTIVES ARE: To study the structure of the antibody combining region primarily by chemical, physical, and also by genetic approaches. We will determine the extent of the combining region complementary to antigen in known crystalline myeloma proteins with polyfunctional combining regions. We will prepare crystalline Fab-hapten complexes with diverse haptens and subject them to X-ray crystallography. In as yet uncrystallized myeloma proteins in solution, we will study the distance between subsites within the combining region which bind diverse haptens. We will use hapten-spacer-dextran probes for this purpose. We will correlate the combining region structure of polyfunctional hapten induced antibodies with those of myeloma proteins having the same hapten specificity. This work studies the central question whether or not the antibody combining region is a mosaic to which many structurally dissimilar haptens can bind. We will use polyfunctional antibodies as V region genetic markers to study V region expression and the translocation of V onto C regions. These studies employ organic synthesis, ampholyte gel isoelectric focusing techniques and radioautography. Other immunochemical studies not directly related to the combining region include: Determination of the primary structure of a new type of human heavy chain disease immunoglobulin fragment containing an insertion; Determining the role of a hitherto unsuspected template protein involved in polymeric IgA and IgM assembly.